document

Metabolomics (liver and blood profiling) in a mouse model in response to fasting: A study of hepatic steatosis

van Ginneken, V. (author), Verhey, E. (author), Poelmann, R. (author), Ramakers, R. (author), van Dijk, K.W. (author), Ham, L. (author), Voshol, P. (author), Havekes, L. (author), van Eck, M. (author), van der Greef, J. (author), TNO Kwaliteit van Leven (author)

A metabolomic approach was applied to a mouse model of starvation-induced hepatic steatosis. After 24 h of fasting it appears that starvation reduced the phospholipids (PL), free cholesterol (FC), and cholesterol esters (CE) content of low-density lipoproteins (LDL). In liver lipid profiles major changes were observed using different techniques....

article 2007

document

Anti-atherosclerotic effect of amlodipine, alone and in combination with atorvastatin, in APOE*3-Leiden/hCRP transgenic mice

TNO Kwaliteit van Leven (author), Trion, A. (author), Maat, M.de (author), Jukema, W. (author), Maas, A. (author), Offerman, E. (author), Havekes, L. (author), Szalai, A. (author), Laarse, A.V.D. (author), Princen, H. (author), Emeis, J. (author)

We investigated the pleiotropic effects of a calcium antagonist (amlodipine) on early atherosclerosis development in the presence and absence of an HMG-CoA-reductase inhibitor (atorvastatin) in apolipoprotein E*3-Leiden/human C-reactive protein (E3L/CRP) transgenic mice. Male E3L/CRP transgenic mice were fed a cholesterol-containing diet either...

article 2006

document

Increased clearance explains lower plasma levels of tissue-type plasminogen activator by estradiol: Evidence for potently enhanced mannose receptor expression in mice

Lansink, M. (author), Jong, M. (author), Bijsterbosch, M. (author), Bekkers, M. (author), Toet, K. (author), Havekes, L. (author), Emeis, J. (author), Kooistra, T. (author), Gaubius instituut TNO (author)

Several clinical studies have demonstrated an inverse relationship between circulating levels of estrogen and tissue-type plasminogen activator (t-PA). The present study was designed to test the hypothesis that estrogen lower plasma levels of t-PA by increasing its clearance from the bloodstream. 17α-Ethinyl estradiol (EE) treatment resulted in...

article 1999

document

Atherosclerosis in APOE(*)3-Leiden transgenic mice from proliferative to atheromatous stage

Lutgens, E. (author), Daemen, M. (author), Kockx, M. (author), Doevendans, P. (author), Hofker, M. (author), Havekes, L. (author), Wellens, H. (author), de Muinck, E.D. (author), Gaubius instituut TNO (author)

Background - This study documents (1) the progression of atherosclerosis along the entire arterial tree in APOE(*)3-Leiden mice after 1, 4, 6, 9, and 12 months of a high-fat/high-cholesterol (HFC) diet and (2) the amount and phenotype of DNA-synthesizing and apoptotic cells in different lesion types after 6 months of HFC diet. Methods and...

article 1999

document

Feasibility of a recombinant human apolipoprotein E reference material

Schiele, F. (author), Barbier, A. (author), Visvikis, A. (author), Aggerbeck, L. (author), Rosseneu, M. (author), Havekes, L. (author), Huttinger, M. (author), Profilis, C. (author), Siest, G. (author), Gaubius Instituut TNO (author)

The aim of this work was to prepare a recombinant apo E material and to determine its suitability as a reference material. We produced human apo E3 using recombinant DNA technology. The cDNA of human apo E3 was cloned in the pARHS bacterial expression vector and used to transfect E. Coli BL21 (DE3) cells. The recombinant protein was then...

article 1998

document

Adenovirus mediated overexpression of human phospholipid transfer protein alters plasma HDL levels in mice

Gaubius Instituut TNO (author), Ehnholm, S. (author), van Dijk, K.W. (author), van Hof, B. (author), van Zee, A.D. (author), Olkkonen, V.M. (author), Jauhiainen, M. (author), Hofker, M. (author), Havekes, L. (author), Ehnholm, C. (author)

To study the function of plasma phospholipid transfer protein (PLTP) in vivo, a liver directed adenoviral gene transfer system was used to overexpress human PLTP in mice. For the experiments, two strains of mice, wild type (C57/B1) and mice transgenic for the human apoA-I gene (HuApoA- ITg), were utilized. Five days after injection of the...

article 1998

document

Modulation of pharmacokinetic behavior of liposomes

Scherphof, G.L. (author), Velinova, M. (author), Kamps, J. (author), Donga, J. (author), van der Want, H. (author), Kuipers, F. (author), Havekes, L. (author), Daemen, T. (author), TNO Preventie en Gezondheid (author)

The authors's recent work on matters pertinent to the in vivo processing of systemically administered liposomes is reviewed. particular emphasis is given to factors influencing blood clearance rates, hepatic and splenic uptake and intrahepatic as well as intrasplenic distribution. In addition to size, liposomal composition plays a crucial role...

article 1997

document

Fibrinogen and atherosclerosis: A study in transgenic mice

Koopman, J. (author), Maas, A. (author), Rezaee, F. (author), Havekes, L. (author), Verheijen, J. (author), Gijbels, M. (author), Haverkate, F. (author), Gaubius Instituut TNO (author)

Atherosclerosis is a multifactorial disease that is influenced by both genetic and environmental factors. Recent epidemiological studies have shown that the combination of elevated VLDL/LDL concentrations and elevated fibrinogen levels results in a strong increase of the risk for cardiovascular disease as compared to the individual risk factors....

article 1997

document

The effect of 26 years of habitual fish consumption on serum lipid and lipoprotein levels (The Zutphen Study)

Kromhout, D. (author), Katan, M.B. (author), Havekes, L. (author), Groener, A. (author), Hornstra, G. (author), de Lezenne Coulander, C. (author), Gaubius Instituut TNO (author)

An inverse association was found between fish consumption and coronary heart disease in the Zutphen Study. In the present study the long-term effects of a small amount of fish on serum lipids and lipoproteins was investigated. Forty healthy, elderly men whose fish consumption pattern over the previous 26-year period was known, were selected for...

article 1996

document

Genetic analysis of sex and generation differences in plasma lipid, lipoprotein, and apolipoprotein levels in adolescent twins and their parents

Boomsma, D.I. (author), Kempen, H.J.M. (author), Gevers Leuven, J.A. (author), Havekes, L. (author), de Knijff, P. (author), Frants, R.R. (author), TNO Preventie en Gezondheid (author)

In a sample of Dutch families consisting of parents aged 35-65 years and their twin offspring aged 14-21 years, a significant difference between generations was observed in phenotypic variances and in genetic heritabilities for plasma levels of total cholesterol, triglycerides, high density lipoprotein (HDL) and low density lipoprotein (LDL)...

article 1996

document

Fibrinogen and atherosclerosis: A study in transgenic mice

Koopman, J. (author), Havekes, L. (author), Verheijen, J. (author), Gijbels, M. (author), Haverkate, F. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)

Atherosclerosis is a multifactorial disease that is influenced by both genetic and environmental factors. Recent epidemiological studies have shown that the combination of elevated VLDL/LDL concentrations and elevated fibrinogen levels results in a strong increase of the risk for cardiovascular disease as compared to the individual risk factors....

article 1996

document

Het karakteriseren van puntmutaties in het low-density lipoproteïne gen in Nederlandse patiënten met heterozygote familiaire hypercholesterolemie

Lombardi, P. (author), Sijbrands, E. (author), Defesche, J. (author), Kastelein, J. (author), Frants, R. (author), Havekes, L. (author), TNO Preventie en Gezondheid (author)

bookPart 1995

document

Een landelijk opsporingsprogramma voor personen met erfelijke hypercholesterolemie, met behulp van moleculaire diagnostiek

Defesche, J. (author), Brink, H. (author), van Zijl, A. (author), Lombardi, P. (author), Havekes, L. (author), Kastelein, J. (author), TNO Preventie en Gezondheid (author)

bookPart 1995

document

Genomic and cDNA cloning of a novel mouse lipoxygenase gene

Willems van Dijk, K. (author), Steketee, K. (author), Havekes, L. (author), Frants, R. (author), Hofker, M. (author), TNO Preventie en Gezondheid (author)

A novel 12- and 15-lipoxygenase related gene was isolated from a mouse strain 129 genomic phage library in a screen with a human 15-lipoxygenase cDNA probe. The complete genomic sequence revealed 14 exons and 13 introns covering 7.3 kb of DNA. The splice junctions were verified from the cDNA sequences of a series of overlapping RT-PCR products....

article 1995

document

ApoE polymorphism and predisposition to coronary heart disease in youths of different European populations; the EARS study. [European Atherosclerosis Research Study]

Tiret, L. (author), de Knijff, P. (author), Menzel, H.J. (author), Ehnholm, C. (author), Nicaud, V. (author), Havekes, L. (author), TNO Preventie en Gezondheid (author)

article 1994

document

Genomic cloning of the mouse LDL receptor related protein/_2-macroglobulin receptor gene

van der Zee, A. (author), Stas, L. (author), Hilleker, C. (author), van Leuven, F. (author), van Dijk, K.W. (author), Havekes, L. (author), Frants, R.A. (author), Hofker, M.H. (author), TNO Preventie en Gezondheid (author)

The LDL receptor-related protein (LRP) or alpha 2-macroglobulin receptor (A2mr) is encoded by a 15-kb mRNA in mouse and human. Probes encompassing different regions of the mouse cDNA were used to isolate clones from a cosmid library of mouse strain 129. Four overlapping cosmids were used for restriction mapping and Southern blot analysis. This...

article 1994

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Postprandial lipoprotein metabolism in normolipidemic men with and without coronary artery disease

Groot, P.H.E. (author), van Stiphout, W.A. (author), Krauss, X.H. (author), Jansen, H. (author), van Tol, A. (author), van Ramshorst, E. (author), Chin-On, S. (author), Hofman, A. (author), Cresswell, S.R. (author), Havekes, L. (author), Gezondheidsorganisatie TNO Gaubius instituut TNO (author)

article 1991

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Mutaties in het LDL-receptor gen in familiaire hypercholesterolemie

Top, B. (author), Frants, R.R. (author), Gevers Leuven, J.A. (author), Havekes, L. (author), Gaubius Instituut TNO (author)

bookPart 1988

document

The effect of ketoconazole, a cytochrome P450 blocker, on hepatic cholesterol metabolism: Abstract

Kempen, H.J. (author), Cohen, L. (author), Havekes, L. (author), Princen, H. (author), Gaubius instituut TNO (author)

conference paper 1986

document

The apolipoprotein E polymorphism at the DNA-level: abstract

Gezondheidsorganisatie TNO Gaubius Instituut TNO (author), Havekes, L. (author), Smit, M. (author), Klasen, E. (author)

article 1986